Background: A primary complaint of chronic fatigue syndrome (CFS) patients is post-exertion malaise, which is a worsening of symptoms following activities such as exercise.

Purpose: To examine the link between gene expression for metabolite, adrenergic, immune, and glucocorticoid receptors on leukocytes and symptoms (pain, fatigue, and mood) following a maximal exercise test.

Results: This comparison of CFS and healthy participants resulted in a significant multivariate main effect for Group (p < 0.05). Univariate analyses indicated group differences for adrenergic α-2A and glucocorticoid (NR3C1) receptor messenger ribonucleic acid and symptoms of fatigue and confusion. Changes in gene expression were significantly correlated with symptoms.

Conclusions: Results suggest that increased glucocorticoid sensitivity may contribute to the symptoms of post-exertion malaise in CFS. As NR3C1 interacts with other transcription factors, investigating the resulting cascades may lead to greater understanding of the biological mechanism of post-exertion malaise. This finding, if confirmed, could lead to novel approaches to prevent symptom exacerbation in CFS.